Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

Amina Jindani; Daniel Atwine; Daniel Grint; Boubacar Bah; Jack Adams; Eduardo Rómulo Ticona; Bhabana Shrestha; Tefera Agizew; Saeed Hamid; Bushra Jamil; Adolf Byamukama; Keneth Kananura; Ivan Mugisha Taremwa; Maryline Bonnet; Lansana Mady Camara; Oumou Younoussa Bah-Sow; Kindy Sadio Bah; Nene Mamata Bah; Maimouna Sow; César Eduardo Ticona Huaroto; Raquel Mugruza Pineda; Bijesh Tandukar; Bijendra Bhakta Raya; Neko Shrestha; Anikie Mathoma; Unami P Mathebula-Modongo; Joyce Basotli; Muhammad Irfan; Dilshad Begum; Ammara Muzammil; Imran Ahmed; Rumina Hasan; Marcos V Burgos; Faisal Sultan; Mariam Hassan; Iqra Masood; Claire Robb; Jonathan Decker; Sisa Grubnic; Philip D Butcher; Adam Witney; Jasvir Dhillon; Tulika Munshi; Katherine Fielding; Thomas S Harrison; RIFASHORT Study Grp

doi:10.1056/EVIDoa2300054

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Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

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Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis

Amina Jindani, Daniel Atwine, Daniel Grint, Boubacar Bah, Jack Adams, Eduardo Rómulo Ticona, Bhabana Shrestha, Tefera Agizew, Saeed Hamid, Bushra Jamil, …

NEJM evidence, Vol.2(9), p.EVIDoa2300054

09/2023

DOI: https://doi.org/10.1056/EVIDoa2300054

PMID: 38320155

Résumé

Antitubercular Agents - adverse effects

Drug Therapy, Combination

Humans

Isoniazid - therapeutic use

Rifampin - adverse effects

Tuberculosis, Pulmonary - chemically induced

BACKGROUND: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS: We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS: Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

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Titre: Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis
Créateurs - sans rôle: Amina Jindani - Institute for Infection and Immunity, St. George's, University of London, London
Daniel Atwine - Mbarara University of Science and Technology
Daniel Grint - London School of Hygiene and Tropical Medicine, London
Boubacar Bah - Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea
Jack Adams - Institute for Infection and Immunity, St. George's, University of London, London
Eduardo Rómulo Ticona - Hospital Nacional Dos de Mayo, Universidad Nacional Mayor de San Marcos, Lima, Peru
Bhabana Shrestha - German Nepal TB Project (GENETUP)/Nepal Anti TB Association (NATA), Kathmandu, Nepal
Tefera Agizew - University of Botswana, Gaborone, Botswana
Saeed Hamid - Aga Khan University Hospital, Karachi, Pakistan
Bushra Jamil - Aga Khan University Hospital, Karachi, Pakistan
Adolf Byamukama - Epicentre/Mbarara Research Base, Mbarara, Uganda
Keneth Kananura - Epicentre/Mbarara Research Base, Mbarara, Uganda
Ivan Mugisha Taremwa - Epicentre/Mbarara Research Base, Mbarara, Uganda
Maryline Bonnet - University of Montpellier, Recherche translationelles sur le virus de l'immunodéficience humaine et les maladies infectieuses, Institut de recherche pour le developpement, Institut national de la santé et de la recherche médicale, Montpellier, France
Lansana Mady Camara - Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea
Oumou Younoussa Bah-Sow - Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea
Kindy Sadio Bah - Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea
Nene Mamata Bah - Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea
Maimouna Sow - Centre Hospitalier Universitaire Ignace Deen, Conakry, Guinea
César Eduardo Ticona Huaroto - Hospital Nacional Dos de Mayo, Universidad Nacional Mayor de San Marcos, Lima, Peru
Raquel Mugruza Pineda - Hospital Nacional Dos de Mayo, Universidad Nacional Mayor de San Marcos, Lima, Peru
Bijesh Tandukar - German Nepal TB Project (GENETUP)/Nepal Anti TB Association (NATA), Kathmandu, Nepal
Bijendra Bhakta Raya - German Nepal TB Project (GENETUP)/Nepal Anti TB Association (NATA), Kathmandu, Nepal
Neko Shrestha - German Nepal TB Project (GENETUP)/Nepal Anti TB Association (NATA), Kathmandu, Nepal
Anikie Mathoma - University of Botswana, Gaborone, Botswana
Unami P Mathebula-Modongo - University of Botswana, Gaborone, Botswana
Joyce Basotli - University of Botswana, Gaborone, Botswana
Muhammad Irfan - Aga Khan University Hospital, Karachi, Pakistan
Dilshad Begum - Aga Khan University Hospital, Karachi, Pakistan
Ammara Muzammil - Aga Khan University Hospital, Karachi, Pakistan
Imran Ahmed - Aga Khan University Hospital, Karachi, Pakistan
Rumina Hasan - Aga Khan University Hospital, Karachi, Pakistan
Marcos V Burgos - Division of Infectious Diseases, University of New Mexico, Albuquerque, NM
Faisal Sultan - Shaukat Khanum Research Centre and Cancer Hospital, Lahore, Pakistan
Mariam Hassan - Shaukat Khanum Research Centre and Cancer Hospital, Lahore, Pakistan
Iqra Masood - Shaukat Khanum Research Centre and Cancer Hospital, Lahore, Pakistan
Claire Robb - Institute for Infection and Immunity, St. George's, University of London, London
Jonathan Decker - Department of Respiratory Sciences, University of Leicester, Leicester, United Kingdom
Sisa Grubnic - Clinical Academic Group in Infection and Immunity, St. George's University Hospitals National Health Service Foundation Trust, London
Philip D Butcher - Institute for Infection and Immunity, St. George's, University of London, London
Adam Witney - Institute for Infection and Immunity, St. George's, University of London, London
Jasvir Dhillon - Institute for Infection and Immunity, St. George's, University of London, London
Tulika Munshi - Institute for Infection and Immunity, St. George's, University of London, London
Katherine Fielding - London School of Hygiene and Tropical Medicine, London
Thomas S Harrison - Medical Reserach Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom
RIFASHORT Study Grp
Détails de publication: NEJM evidence, Vol.2(9), p.EVIDoa2300054
Note de subvention: MR/R010161/1 / Medical Research Council MR/V033417/1 / Medical Research Council
Identifiants: 99158641109311
Unité académique: Recherches translationnelles sur le VIH et les Maladies Infect. Endém. émerg. - TransVIHMI
Langue: English
Type de ressource: Journal article